基因组调控区遗传变异与胃癌易感性的关联研究

《基因组调控区遗传变异与胃癌易感性的关联研究》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、１分类号：Ｒ８单位代码：１０３１２：密级学号：２０１５１２０８馨南京＆种：硕士学位论文题目：基因组调控区遗传变异与胃癌易感性的关联研究研究生：俞飞指导教师：靳光付教授学科专业：流行病与卫生统计学学院名称：公共卫生学院二〇一完成时间：八年五月目录一、中文摘要··················································································1二、英文摘要······································

2、············································4三、论文正文··················································································7前言························································································7材料与方法···············································

3、······························10结果······················································································20讨论······················································································34总结·······························································

4、·······················37参考文献················································································38四、综述······················································································47五、附录······································································

5、················64附录一、论文缩略词表······························································64附录二、个人简介和发表论文·····················································65六、致谢······················································································68南京医科大学硕士学位论文基因组调控区遗传变异与胃癌

6、易感性的关联研究中文摘要【研究背景】胃癌是世界范围内发病率和死亡率均较高的恶性肿瘤。环境因素和遗传因素在胃癌的发生中均发挥着重要的作用，已知的环境危险因素主要包括幽门螺杆菌感染，EB病毒感染，蔬菜水果摄入不足，腌制食品摄入，吸烟以及肥胖等，大型双生子研究发现胃癌的遗传度为22%。全基因组关联研究（GWAS）是研究复杂疾病遗传易感机制的有力工具，目前胃癌GWAS共发现了11个遗传易感位点，然而，这些胃癌相关遗传变异仅能解释胃癌一小部分的遗传度，这种遗传度缺失的现象的可能是由于传统的GWAS对显著性水平要求比较严格，忽略了很多潜在的易感位点，因此，还需

7、进一步探索基因组上与胃癌易感性相关的遗传变异。研究发现，尽管GWAS发现了大量与疾病或性状相关的遗传位点，但绝大部分的位点位于非编码序列。DNA元件百科全书（ENCODE）计划揭示非编码序列在基因调控中发挥重要作用。随后，越来越多的研究表明GWAS发现的位于非编码区的遗传易感位点可通过远程调控靶基因功能影响疾病的发生。脱氧核糖核酸酶I超敏感位点（DHS）作为一种基因组调控区域的标记，可以敏感标记基因组上顺式调控元件，包括启动子、增强子、绝缘子、沉默子等。研究发现，GWAS发现的与疾病或性状相关的非编码区遗传变异显著富集于DHS，提示调控区遗传变异是

8、影响复杂疾病或性状的重要遗传机制。因此，本研究拟以胃癌GWAS数据为基础系统探讨基因组调控区遗传变异与胃癌易感性之间的关联